1/7. Neonatal diabetes mellitus, congenital hypothyroidism, hepatic fibrosis, polycystic kidneys, and congenital glaucoma: a new autosomal recessive syndrome?We report on two sibs (of 4) with a syndrome of minor facial anomalies, proportionate IUGR, neonatal non-autoimmune diabetes mellitus (NDM), severe congenital hypothyroidism (CH), cholestasis, congenital glaucoma, and polycystic kidneys. liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the two sibs was identical. Although a combination of liver, kidney, and pancreatic involvement has been described in Ivemark syndrome (hepato-renal-pancreatic syndrome), the coexistence of NDM, CH, and glaucoma in both sibs suggests the possibility that this combination of manifestations describes a new autosomal recessive syndrome. mutation analysis for several candidate genes is warranted.- - - - - - - - - - ranking = 1keywords = cholestasis (Clic here for more details about this article) |
2/7. biliary atresia due to delayed maturation of the gut hormones' system?--Introducing a new treatment modality.BACKGROUND: Congenital biliary atresia is suspected to originate from prenatal biliary duct inflammation of unknown etiology. OBJECTIVE: Based on clinical grounds, we aimed to establish a hypothesis on the primary cause of inflammation, and to suggest a causal treatment modality. CASE REPORT: history. A 28 years old Turkish woman had lost her first child aged two years from congenital biliary atresia (parents second degree cousins). After a miscarriage, in her otherwise uneventful third pregnancy sonography at 34 wks revealed echogenic material in the fetal gallbladder. Nine days later the gallbladder was completely filled with sludge. Chemical inflammation was suspected, and birth was induced at 36 3 weeks in order to allow for surgical flushing of the bile duct. Neonatal clinical chemistry was insuspicious. There was no spontaneous resolution of the sludge within the first 24 hours of life. A trial of medical treatment with intermittent i.v. secretin (0.03 CU/kg/h) and i.v. coeruletid (60 ng/kg/h) was started. Within 24 hours, sludge had resolved. CONCLUSIONS: We hypothesize that dysmaturation may lead to insufficient induction/production/activity of intrinsic gut hormones resulting in prenatally impaired bile flow, or even inspissated bile. Familial occurrence suggests a genetic defect. Exogenous hormone therapy might be an appropriate treatment modality.- - - - - - - - - - ranking = 0.0060571291663254keywords = bile (Clic here for more details about this article) |
3/7. Conformational Asn187Asp/Lys antithrombin variants and thrombosis. Clinical and biological features in 13 new heterozygotes.Antithrombin Rouen VI (N187D) is a rare conformational thermolabile variant. The unique symptomatic carrier reported in the literature developed 3 thrombotic events during pregnancy, in each case in a context of pyrexial infection. In fresh plasma, antithrombin activity and antigen level were normal but in vitro experiments demonstrated the presence of a thermolabile variant, suggesting that fever could be a trigger for thrombosis in N187D carriers. The RouenVI variant was further found in two asymptomatic brothers. In these subjects, it was associated with normal antigen level but reduced activity. In order to better delineate the functional and clinical consequences of the N187 variants, we have studied a series of seven subjects from two distinct families heterozygous for the Rouen VI mutation. Antithrombin levels were normal or borderline in these patients. Thermostability of plasma antithrombin was normal. We have also studied six subjects heterozygous for a new mutation, 6462C>G,which results in an asparagine to lysine substitution at residue 187. In these patients, the N187K mutation is associated with a clear type II deficiency and decreased thermostability of the plasma protein has been demonstrated. That the N187D mutation has milder consequences on plasma antithrombin activity than the N187K mutation is in agreement with structural predictions. About 50% of the N187 carriers studied have suffered venous thrombotic events, strongly suggesting that both mutations are risk factors for thrombosis, but none occurred during pyrexial infections.- - - - - - - - - - ranking = 0.0040380861108836keywords = bile (Clic here for more details about this article) |
4/7. Reversible nitrous oxide myelopathy and a polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase.We present a case of a patient who received nitrous oxide on two occasions within a period of 8 weeks and who subsequently developed a diffuse myelopathy, characterized by upper extremity paresis, lower extremity paraplegia and neurogenic bladder. Laboratory testing revealed hyperhomocysteinaemia and low levels of vitamin B(12). Because of this uncommon clinical presentation, we analysed the patient's dna, and found a polymorphism in the MTHFR gene that is associated with the thermolabile isoform of the 5,10-methylenetetrahydrofolate reductase enzyme, which explained the myelopathy experienced by the patient after being exposed to nitrous oxide. Soon after initiating supplementary therapy with folic acid and vitamin B(12), the neurological symptoms subsided.- - - - - - - - - - ranking = 0.0020190430554418keywords = bile (Clic here for more details about this article) |
5/7. prenatal diagnosis of inherited epidermolysis bullosa in a patient with no family history: a case report and literature review.OBJECTIVE: The junctional form of epidermolysis bullosa (EB) is a recessively inherited mechanobullous disease in which minimal trauma results in blister formation at the dermal-epidermal junction. A rare form associated with pyloric atresia (JEB-PA) is a severe clinical subtype leading to rapid demise after birth, thus justifying prenatal diagnosis. The case characterized by abnormal ultrasound findings at 35 weeks of gestation (gastric dilatation associated with polyhydramnios) of a patient with no family history is reported. METHOD: Postabortion skin biopsies were analyzed by immunofluorescence that revealed marked reduction of integrin alpha6beta4 in accordance with the diagnosis of JEB-PA. RESULTS: amniotic fluid contained excess total protein (4 MoM), abnormally high AFP (20.4 MoM) related to skin lesions and abnormally elevated digestive enzyme suggestive of fetal vomiting of bile. The electrophoretic pattern of cholinesterases was unusual (additional slow band). Maternal serum AFP was 3.14 MoM and free beta-hCG 13.1 MoM. Because of these concomitant findings, JEB-PA was suspected. CONCLUSION: The case under study was atypical because of late clinical manifestations of the disease: polyhydramnios, gastric enlargement. As maternal serum AFP at 15 weeks may be normal, it was suggested that discovery of polyhydramnios during the second or the third trimester should prompt biochemical analysis of amniotic fluid, such as AFP and GGTP assay in all cases.- - - - - - - - - - ranking = 0.0020190430554418keywords = bile (Clic here for more details about this article) |
6/7. Four primary malignancies successively occurred in a BRCA2 mutation carrier: a case report.Carriers of BRCA2 germline mutation have a significantly increased lifetime risk of breast and ovarian cancer compared to non carriers. Several other carcinomas seem to be associated with BRCA2 mutations: pancreas, prostate, larynx, gallbladder, bile duct cancer, and malignant melanoma. We described a case of a 67-year-old BRCA2 mutation carrier of Caucasian, non-Jewish, ethnic origin who successively developed 4 primary malignancies in 30 months: breast ductal carcinoma, chronic lymphatic leukemia, ovarian serous papillary carcinoma, and endocervical adenocarcinoma. This is the first case of 4 primary malignancies in a BRCA mutation carrier, also occurred in such a short observation period. Chronic lymphatic leukemia and endocervical adenocarcinoma have not been yet associated to BRCA2 germline mutation.- - - - - - - - - - ranking = 0.0020190430554418keywords = bile (Clic here for more details about this article) |
7/7. Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and intrahepatic cholestasis of pregnancy.Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus and elevated bile acid serum concentrations in late pregnancy. Splicing mutations have been described in the multidrug resistance p-glycoprotein 3 (MDR3, ABCB4) gene in up to 20% of ICP women. Pedigrees studied were not large enough for linkage analysis. Ninety-seven family members of a woman with proven ICP were asked about pruritus in earlier pregnancies, birth complications and symptomatic gallstone disease. The familial cholestasis type 1 (FIC1, ATP8B1) gene, bile salt export pump (BSEP, ABCB11) and MDR3 gene were analyzed in 55 relatives. We identified a dominant mode of inheritance with female restricted expression and a new intronic MDR3 mutation c.3486 5G>A resulting in a 54 bp (3465-3518) inframe deletion via cryptic splicing site activation. Linkage analysis of the ICP trait versus this intragenic MDR3 variant yielded a lod score of 2.48. A Bayesian analysis involving MDR3, BSEP, FIC1 and an unknown locus gave a posterior probability of >0.9966 in favor of MDR3 as causative ICP locus. During the episode of ICP the median gamma-glutamyl transpeptidase (gamma-GT) activity was 10 U/l (95% CI, 6.9 to 14.7 U/l) in the index woman. Four stillbirths were reported in seven heterozygous women (22 pregnancies) and none in five women (14 pregnancies) without MDR3 mutation. Symptomatic gallstone disease was more prevalent in heterozygous relatives (7/21) than in relatives without the mutation (1/34), (P = 0.00341). CONCLUSION: This study demonstrates that splicing mutations in the MDR3 gene can cause ICP with normal gamma-GT and may be associated with stillbirths and gallstone disease.- - - - - - - - - - ranking = 32.686742465533keywords = intrahepatic cholestasis, cholestasis, intrahepatic, bile (Clic here for more details about this article) |